System for withdrawing small amounts of body fluid

ABSTRACT

System for withdrawing small amounts of body fluid comprising a drive unit which has a holder which is moved from a first into a second position when the drive unit is activated, and a disposable lancing unit which has a holding area that is removably positioned in the holder, the proximal end of an elongate capillary structure comprising at least one capillary channel for transporting body fluid being connected to the holding area and the distal end of the capillary structure being suitable for piercing skin, wherein the distal end of the capillary structure is located outside the skin when the holder is arranged in a first position and in the second position is inserted into the skin up to the puncture depth, characterized in that the at least one capillary channel is open to the outside in an area which comprises at least a part of the longitudinal extension of the capillary structure.  
     Disposable lancing unit for removing small amounts of body fluid which has a holding area to which the proximal end of an elongate capillary structure is connected to comprising at least one capillary channel to transport body fluid and the distal end of the capillary structure is suitable for piercing skin, characterized in that an area of the at least one capillary channel which comprises at least a part of the longitudinal extension of the capillary structure is open to the outside.

[0001] The present invention relates to the field of body fluid analysesin order to make a diagnosis or to monitor the concentration ofmetabolic parameters such as the blood glucose concentration.

[0002] The invention concerns a system for withdrawing small amounts ofbody fluid comprising a drive unit with a holding device for adisposable lancing unit which has a holding area and a capillarystructure connected to the holding area. The capillary structure has atleast one capillary channel and a tip for piercing the skin which facesaway from the holding device. At least a part of the longitudinalextension of the capillary structure is open towards the outside.

[0003] Systems for withdrawing body fluids are already known in theprior art in which the body fluid is taken up into a disposable element.Blood collection and analytical systems are known from the document EP 0199 484 which comprise a disposable unit with a capillary to collectbody fluid and transport the body fluid into a detection area. Thefurther development of this concept is described in WO 97/42888. Thearrangement described herein is particularly suitable for collectingrelatively small amounts of body fluids which is primarily accomplishedby pressing a ring onto the area surrounding a collection site and apumping movement. A system for analysis based on small amounts ofinterstitial fluid is known from EP 0 723 418. For this purpose a verythin closed hollow needle is inserted into the dermis and interstitialfluid is conveyed through the needle to a test zone by applying pressureto the area surrounding the puncture site. A highly miniaturizedarrangement which also utilizes a closed needle to withdraw body fluidis known from U.S. Pat. No. 5,801,057. A particular advantage of thisarrangement is the extremely thin needle which can be inserted at leastinto the arm region of a patient without essentially any pain.

[0004] Whereas the arrangement described in U.S. Pat. No. 5,801,057already fulfils numerous practical requirements, some features are inneed of improvement. A general problem with the sampling devicesaccording to the previously mentioned document is to manufacture thehollow needle cost-effectively and as small as possible. Miniaturizationwhich is in particular desirable with regard to minimizing the paincaused by the lancing process and minimizing the size of the puncturewound results in high manufacturing costs for the very thin closedneedles and there are additional fundamental feasibility problems.

[0005] According to the present invention the requirements for systemsfor withdrawing small amounts of body fluids are met using needles withan open capillary structure instead of the closed needle designs knownin the prior art. This not only results in considerable advantages forthe manufacturing process by making it possible to manufacture thesampling system in a cost-effective and simple manner, but it alsoresults in major advantages in the collection of body fluids since thisdoes not only occur through the cannula tip of the hollow needle as inthe case of closed needle designs but also through the open area of thecapillary structure. Moreover one can also utilize the advantage thatthe open channel area of the needle, even when it is still inserted, isable to collect blood from the skin surface and transport it to adetection zone.

[0006] One particular field of application of systems for withdrawingsmall amounts of body fluid is the so-called spot-monitoring in whichthe concentration of particular analytes present in the body fluids isdetermined at a particular time. Such measurements can be carried outrepeatedly at time intervals in order to monitor a change of the analyteconcentration. Such an analysis using disposable test elements hasproven to be particularly advantageous especially in the field of bloodsugar measurement by diabetics. If excessively high blood sugar values(hyperglycaemia) occur in a diabetic over a certain period of time, thiscan lead to serious long-term damage such as blindness and gangrene. If,on the other hand, a diabetic falls into a state of hypoglycaemiabecause he has for example injected too large a dose of insulin, thiscan become life-threatening if the diabetic falls into a so-calledhypoglycaemic shock. In contrast a regular control of the blood sugarlevel enables the diabetic to avoid hyperglycaemic and hypoglycaemicstates and also permanently learn how to coordinate his eating habits,bodily activity and insulin medication. In addition to improving andmaintaining the health of diabetics, regular blood sugar monitoring alsohas considerable overall economic advantages since the high costs forsecondary diseases can be avoided. The reasons which prevent a morewidespread and consequent use of blood sugar monitoring are primarilythe pain caused by the required body fluid collection and the extensivehandling steps of the common systems in the market. With the currentwidely used systems the diabetic or medical staff must firstly obtain adrop of blood which is usually from the finger pad. If this is to becarried out with as little pain as possible, so-called lancing devicesare used. A lancing device must be firstly loaded with a lancet,tensioned, placed on the body surface and triggered. After the lancingprocess the user has to knead his finger in order to convey a drop ofblood out of the puncture wound which should be as small as possible.Before this procedure the diabetic has to already place a test strip ina blood sugar measuring instrument and activate it. The drop of bloodcan now be applied to the test strip and after for example 10 seconds ablood sugar measurement is available. The user now has to also disposeof the spent lancet and test strip. The present invention enables theprocess of blood sugar measurement to be greatly simplified by providinga so-called integrated system in which only one(disposable) unit carriesout the lancing, sampling and analytical reaction.

[0007] A system according to the invention serves to withdraw smallamounts of body fluid. In this context body fluids are understood inparticular as blood, interstitial fluid and mixtures of these bodyfluids. Whereas in conventional systems for blood collection this isusually carried out on the finger pad, the collection system accordingto the invention can also be used to withdraw blood from other sites onthe body such as the forearm.

[0008] A disposable lancing unit for withdrawing small amounts of bodyfluid according to the invention has a holding area which is connectedto the proximal end of an elongate capillary structure having at leastone capillary channel to transport body fluid. The distal end of thecapillary structure is suitable for piercing skin and at least a part ofthe capillary structure is open to the outside along its longitudinalextension. A capillary structure is understood within the scope of theinvention as a body which transports body fluid as a result of capillaryforces towards the proximal end of the capillary structure when thedistal area is contacted with body fluid. With regard to this functionthe capillary structure according to the invention is similar to thehollow needles described in U.S. Pat. No. 5,801,057 and EP 0 723 418.However, an important difference is that at least one area whichcomprises at least part of the longitudinal extension of the capillarystructure is open to the outside. The longitudinal extension of thecapillary structure extends from the proximal end which is connected tothe holding area to the distal area which is intended to be insertedinto the skin. The hollow needles of the prior art only have an openingat their outermost distal end through which body fluid can enter. Incontrast the capillary structure according to the invention can take upbody fluid over a much larger part of its longitudinal extension. As arule the length of the region of capillary structure which is open tothe outside is more than 10% of the longitudinal dimension of thecapillary structure and preferably more than 50% of the longitudinaldimension. It is particularly advantageous for the manufacturing processwhen the capillary structure is open to the outside along its entirelongitudinal dimension.

[0009] Conventional hollow needles are manufactured in the prior art bydrawing out thicker tubes. It is consequently very laborious and costlyto manufacture very thin hollow needles of for example less than 0.3 mmouter diameter. In contrast U.S. Pat. No. 5,801,057 proposes a differentmethod. A first body which has a needle area with a channel and ameasuring chamber which is integrally connected to the needle is etchedfrom silicon, the measuring chamber and channel are subsequently sealedwith a layer in the area of the needle. The two bodies are for exampleconnected by anodic bonding. The high degree of miniaturization of theblood sampling device and the bonding step in the process result in veryhigh manufacturing costs. Furthermore, the arrangement that is formedaccording to the previously mentioned documents of the prior art canalso only take up liquid via the tip area of the needle. According tothe invention it was found that it is possible to also achieve anefficient uptake of liquid when an open capillary is present. Examplesof such open capillaries are described in the following:

[0010] Open capillaries can be manufactured by photolitho-graphicmethods like those described in the document U.S. Pat. No. 5,801,057 andwhich are known from the field of semiconductor technology. It is alsopossible to provide channels, grooves etc. which are open to the outsidein solid needles by milling, etching and suchlike. Such depressions leadfrom the tip or at least from a region adjoining the tip to the proximalend of the needle which is connected to the holding device. Thesedepressions or capillaries do not necessarily have to run in straightlines, but can also for example be arranged in spirals, meanders etc. Itis important that liquid is transported through the capillaries from thedistal area of the needle into the proximal area. The cross-section ofthe capillaries can for example be V-shaped, semi-circular or alsorectangular. It is important that a part of the cross-section is open tothe outside so that fluid can penetrate into the capillary channelthrough the external peripheral surface of the needle.

[0011] In addition to the already mentioned methods for incorporatingcapillary channels into rod-shaped bodies, it is also possible togenerate the capillary channels by assembling bodies. Thus it is forexample possible to fasten two or more solid needles together forexample by welding such that the contact areas of the solid needles formcapillary channels. In a corresponding manner it is also possible totwist wires together in the form of a stranded wire such that numerouscontact areas are formed which generate the capillary channels.

[0012] The capillary channels which are present in the capillarystructure typically have a greater depth than width. The ratio of depthto width (generally referred to as aspect ratio) is preferably 2 to 5.The cross-section of the capillary channel is typically larger than 2500μm² and less than 1 mm². As already stated above it is advantageous thatthe capillary channels are accessible to the outside such that they canalso take up body fluid while the capillary structure is inserted intotissue. In order to achieve a good uptake of body fluid the area of thecapillary structure that is open to the outside should have a length of1 mm or more.

[0013] The holding area adjoins the proximal part of the capillarystructure. The holding area and capillary structure can be formed as onepiece (monolithic) as well as be separate parts which are connectedtogether by glueing, welding, press fitting or suchlike.

[0014] Monolithic structures can be generated particularlyadvantageously from semiconductors using the known manufacturingprocesses for semiconductors. This can result in a very high degree ofminiaturization. In contrast the manufacturing costs may be morefavourable when the lancing device is manufactured from a separateholding area and a separate capillary structure. A lancing device madeof separate elements can for example be formed from a metallic capillarystructure and a holding area made of plastic.

[0015] The proximal area of the capillary structure or the holding areaof a lancing device according to the invention can have an evaluationzone. If the analyte concentration is for example evaluated by means ofinfrared spectroscopy, the detection zone does not have to containfurther reagents to enable the analyte to be determined. Since thematerials for the capillary structure and the holding area are usuallyimpermeable to infrared light, analysis by reflection spectroscopy ispreferred. For this purpose the evaluation zone can preferably reflectIR light which is usually the case to an adequate extent with metalsurfaces. Plastics can for example be made to reflect IR light by vapourdepositing or sputtering gold or aluminium. (Alternatively opticallytransparent windows can also be integrated).

[0016] However, in the preferred case the lancing unit has a detectionzone in which a reagent is located which undergoes a detectable changeon contact with an analyte to be detected in the sample of body fluid.Typical reagents for detecting glucose are based for example on glucoseoxidase in conjunction with a chromogenic redox system. Reagents arewell known in the prior art for an optical evaluation which form acolour with glucose from the body fluid. Furthermore reagents are alsoknown from the field of blood sugar test strips which allow anelectrochemical detection of an analyte. Since such detection systemsare also well-known from the prior art they are not described in moredetail herein.

[0017] The said reagent systems can be arranged in the proximal area ofthe capillary structure, but since there are no particularly convenientpossibilities for immobilizing and evaluating the reagents in this area,it is preferable to place the reagents in the holding area. In order towet the reagents with body fluid, the reagent either directly adjoinsthe capillary structure and can take up body fluid by its own capillaryforces or a fluid connection (e.g. connecting channel, fleece etc.) canbe provided between the capillary structure and the detection zonethrough which the body fluid can pass from the capillary structure intothe detection zone. The lancing unit can for example be designed suchthat a capillary channel of the capillary structure is extended into theholding area and a reagent in the area of the holding area can beapplied directly to the capillary channel which extends into this area.The reagent mixtures that are used are usually in a solid state and, dueto their constituents (e.g. aluminium oxide, kieselguhr and suchlike),have such a high capillarity that they can take up body fluid from thecapillary channel.

[0018] The shape of the holding area is relatively uncritical. It canfor example be in the form of a small cube which has a depression toreceive the reagent mixture. Special measures are usually not necessaryto mount the lancing unit in a drive unit, or designs can be used thatare known for disposable lancets of conventional blood sampling systems.For example the holding area can have tapers into which spring elementsof a holder of the drive unit engage in order to hold the lancing unit.The lancing unit is advantageously positioned within the holder in sucha manner (for example by pressing the end of the lancing unit facingaway from the tip against a stop) that it allows a good control of thepiercing depth of the lancing unit. Reference is made to the document EPB 0 565 970 with regard to such a holder and the interaction between theholder and the disposable lancing unit.

[0019] In a system for withdrawing small amounts of body fluids it maybe advantageous to integrate a detection unit. If a lancing unitcontaining a reagent is used which changes colour or forms a colour whenan analyte is present, the system can have an optical detection unitcomprising a light source and a detector to detect transmitted orreflected light. If electrochemical detection is used, the system canhave electrodes which contact the reagent of the lancing unit or thecontacts of the lancing unit which in turn contact the reagent. For theevaluation the system can have the electronic devices known in the priorart in order to determine the concentration of the analyte for exampleby measuring the so-called Cotrell current. If it is intended to carryout a reagent-free analysis, the system can for example comprise aninfrared radiation source and an infrared detector and devices for thespectral resolution of the radiation reflected from the evaluation zone.

[0020] The collection system according to the invention additionally hasa drive unit which, when activated, moves the holder from a first into asecond position such that the lancing unit performs a lancing movement.Such drive units are well-known from the field of blood samplingsystems. It can for example contain a spring which is tensioned by theuser and drives the lancing unit when it relaxes. A particularlyadvantageous drive unit is described in EP B 0 565 970.

[0021] With the lancing unit according to the invention or thecollection system according to the invention, body fluid can bewithdrawn while the capillary structure or a part thereof is insertedinto the skin (i.e. withdrawal directly from the body or from body fluidemerging from the body on the body surface) or the capillary structurecan be retracted from the body after the piercing operation and take upbody fluid that emerges from the body surface. A withdrawal in which thecapillary structure remains in the body to collect body fluid isespecially suitable for sampling from the arm. This is due to the factthat small incisions on the arm close again very rapidly such that nofluid or only very small amounts of fluid emerge after the piercing. Onthe other hand the sensitivity to pain is much less pronounced on thearm as compared for example to the finger and thus when the capillarystructure remains in the body this is not felt to be painful. Asdescribed above an advantage of a capillary structure that is open tothe outside compared to conventional hollow needles is that fluid can betaken up through the open area whereas the area for taking up liquids byhollow needles is limited to the front end of the needle. The latter isparticularly disadvantageous when the needle opening becomes sealed bytissue components during the piercing process such that no liquid oronly an inadequate amount can be taken up.

[0022] It also has an advantage over conventional hollow needles in thecase of a withdrawal in which the capillary structure is retracted fromthe tissue after the lancing process. As already described capillarystructures that are open to the outside can be much more simply andcheaply manufactured than closed hollow needles.

[0023] Furthermore a withdrawal process can be carried out with thelancing units according to the invention which is a combination of thepreviously mentioned processes. In this combination process piercing isfirstly carried out, the capillary structure is pulled back over a partof the piercing path and is allowed to reside there for a collectionperiod of several seconds. An advantage of this process is that theretraction of the capillary structure exposes part of the lancingchannel such that body fluid can collect in it and can enter from thereinto the capillary structure.

[0024] A further decisive factor which is important for an efficientuptake of body fluid by means of the capillary structure is thewettability of the capillary channels. If capillary structures made ofsilicon are used, these are usually adequately wettable due to a siliconoxide layer on the surface. If metals are used for the capillarystructure, these are often relatively difficult to wet. This can becounteracted by a number of different measures such as silication of thesurface. The wettability is usually adequate when the liquid in thecapillaries has a concave meniscus which is synonymous with a wettingangle of less than 90°.

[0025] The invention is illustrated in more detail on the basis offigures:

[0026]FIG. 1: Disposable lancing unit made of silicon.

[0027]FIG. 2: System for withdrawing body fluid comprising the lancingunit from FIG. 1, a drive unit and an optical evaluation device.

[0028]FIG. 3: Capillary region of a disposable lancing unit composed of2 solid needles that are welded together.

[0029]FIG. 4: Capillary structure formed from wires that are twistedtogether (stranded wire structure).

[0030]FIG. 5: Capillary structure in the form of a solid needle on thesurface of which capillary channels are located.

[0031]FIG. 1 shows a disposable lancing device in three views. Theperspective view in FIG. 1A shows that the lancing unit 10 has acapillary structure 11 which is arranged in a holding area 12. Theholding area 12 is capped with a plate 13 which has a window 14. Thecapillary structure 11 is designed such that its distal end has a tip inorder to pierce the skin. In addition a capillary channel 15 which isopen at the top is arranged in the capillary structure. This capillarychannel extends further inside the lancing unit and reaches a detectionzone which is arranged below the window 14. The end 15A of the capillarychannel can be seen in the window region in FIG. 1B. In this case theend is visible since there is no test chemistry arranged above thechannel. However, in the ready-to-use state a detection area e.g. anoptical detection system for glucose is arranged above this end.

[0032]FIG. 1C shows a side view of the lancing unit which shows that theside of the capillary channel 15 is open towards the top as well as atthe distal end of the capillary structure. The length of the capillarystructure shown is 1.6 mm and the width and depth of the capillarychannel 15 are 50 and 150 μm respectively.

[0033]FIG. 2 shows a system (20) for withdrawing body fluid whichcomprises a lancing device as shown in FIG. 1, a drive unit and anoptical evaluation device. The figure shows a system which is based on ablood collection device according to EP 1034740. The lancing device ofFIG. 1 is located in the holder of the blood collection device in whicha disposable lancet is arranged in previous systems. The drive mechanismis tensioned by actuating the push-button 21 and the lancing process,i.e. the movement of the lancing device, is triggered by operating therelease button 22. In this process the capillary area 11 emerges from anexit port (not shown) in the cap 23 (shows by the dashed line) andpunctures the skin which is located at the cap opening in order tocollect blood. In contrast to blood lancing devices which arecommercially available under the name Softclix Pro, the capillary regionis not pulled back behind the cap opening but remains over its maximumpiercing depth in the tissue or is partially retracted such thatemerging body fluid can be taken up into the capillary. As shown inconjunction with FIG. 1 body fluid passes through the capillaries intoan evaluation area in which it is possible to determine an analyte. FIG.2 shows an optical evaluation system which comprises a light source 24and a photodetector 25. The evaluation area is illuminated by the lightsource 24 (e.g. a light emitting diode) through the window 14 andradiation reflected from the evaluation area is captured by thephotodetector 25. An analyte concentration is determined by anevaluation unit (not shown) in the system from the intensity received bythe photodetector and displayed on the display 26. After the measurementis completed the user can remove the system 20 from the body surface,remove the cap 23 and eject the lancing unit 10. A new lancing unit canbe inserted into the holder 27 of the system, e.g. from a magazine, fora further measurement.

[0034]FIG. 3 shows the generation of a capillary structure by weldingtwo solid needles. FIG. 3 shows that two opposing capillary channels areformed which are open to the outside by welding two cylindrical metalwires. One end of the structure that is obtained is ground to form a tipwhich enables it to pierce the skin. In the example shown metal wiresmade of medical stainless steel with a cross-section of 400 μm are used.The tip area 11 a of the capillary structure has a length of about 2 mm.The two wires are welded by passing a current through the two wires, onewire being connected as the anode and the other as the cathode.

[0035]FIG. 4 shows a capillary structure in the form of a stranded wire.In order to generate this stranded structure 40, metal wires having adiameter of 20 to 70 μm were twisted together and one end was cut at anoblique angle to result in a tip area 40 a which can pierce the skin.The enlargement in FIG. 4 shows the tip region of the open capillarychannels (indicated by arrows) which are formed by the adjacent wires.

[0036]FIG. 5 shows a capillary structure 50 which has been generatedfrom a solid needle. The needle has a proximal area 50 b which can beheld in a holding area. The tip area 50A of the needle is bevelled likeconventional blood lancets in order to allow a largely painless skinpenetration. The capillary channel 51 which is open to the outside wasmilled into the solid needle. A cross-section of this capillary channelis about 60×150 μm.

1. System for withdrawing small amounts of body fluid comprising a driveunit which has a holder which is moved from a first into a secondposition when the drive unit is activated, and a disposable lancing unitwhich has a holding area that is removably positioned in the holder, theproximal end of an elongate capillary structure comprising at least onecapillary channel for transporting body fluid being connected to theholding area and the distal end of the capillary structure beingsuitable for piercing skin, wherein the distal end of the capillarystructure is located outside the skin when the holder is arranged insaid first position and in said second position is inserted into theskin up to the puncture depth, wherein the at least one capillarychannel is open to the outside in an area which comprises at least apart of the longitudinal extension of the capillary structure.
 2. Systemas claimed in claim 1, in which the entire length of the capillarystructure from the proximal to the distal end is open to the outside. 3.System as claimed in claim 1, in which the holding area has a detectionzone for detecting one or several analytes, the detection zone beingarranged such that it can take up body fluid from the capillarystructure.
 4. System as claimed in claim 1, in which the drive unitmoves the lancing unit in such a manner that it remains in the secondposition for a time interval (collection period) and, subsequently, thelancing unit is moved into a position in which the distal end of thecapillary structure is outside the skin.
 5. System as claimed in claim1, in which the drive unit moves the lancing device in such a mannerthat after reaching the second position it is moved back into acollecting position in which a section of the capillary structurelocated in the skin is shorter than in the second position.
 6. System asclaimed in claim 1, in which the capillary structure and holding areaare integrally connected together.
 7. System as claimed in claim 1 or 6,in which the holding area and capillary structure are manufactured froma semiconductor preferably silicon.
 8. System as claimed in claim 6 or7, in which the holding area and capillary structure are integrallymanufactured from a single piece of material.
 9. System as claimed inclaim 1, in which the area of the capillary structure that is open tothe outside has a channel shape.
 10. System as claimed in claim 9, inwhich the channel-shaped area has an essentially V-shaped cross-section.11. System as claimed in claim 1, in which the length of the capillarystructure is in the range from 0.3 to 3 mm and the cross-section of thecapillary structure is in the range from 0.03 to 0.8 mm.
 12. Disposablelancing unit for withdrawing small amounts of body fluid which has aholding area to which the proximal end of an elongate capillarystructure is connected, said capillary structure comprising at least onecapillary channel to transport body fluid and the distal end of thecapillary structure is suitable for piercing skin, wherein an area ofsaid at least one capillary channel which comprises at least a part ofthe longitudinal extension of the capillary structure is open to theoutside.